IL43915A

IL43915A - Sustained release dispensing device and method of dispensing an active agent

Info

Publication number: IL43915A
Application number: IL4391573A
Authority: IL
Original assignee: Alza Corp
Priority date: 1972-12-27
Filing date: 1973-12-26
Publication date: 1976-08-31
Also published as: IE38672L; JPS4994818A; CH603165A5; DK144825C; AU6380473A; DE2363963B2; NL181627C; IT1055547B; NL7317731A; SE433908B; FR2247259A1; NL181627B; JPS613766B2; FR2247259B1; DE2363963A1; AR206692A1; IE38672B1; GB1417527A; DK144825B; ES421677A1

Claims

Claims:

1. A sustained release dispensing device for dispensing an active agent to an aqueous environment having an essentially constant pH in the range of 6 /to 9 throughout the period of administration comprising an active agent dispersed through a body of a hydrophobic poly(carboxylic acid) having one ionizable carboxylic hydrogen atom for each 8 to 22 carbo atoms, which body when placed in said environment erodes at a controlled rate over a prolonged period of time in response to the essentially constant pH environment by a process of carboxylic hydrogen ionization, thereby releasing the dispersed active agent at a controlled rate over a prolonged period of time.

2. » A sustained release dispensing device in accordance with claim 1 wherein the hydrophobic pol (carboxylic acid) is represented by the formulas wherein the R's represent organic radicals independently eelected to provide an average of from 8 to 22 total carbon atoms for each carboxylic hydrogen atom and n has a value providing an average.molecular weight of from 10,000 to 800,000. . ■ I ■

3. A sustained release dispensing device in accordance with claim 2 wherein n has a value providin an average molecular weight of from 15,000 to 500,000.

4. A sustained release dispensing device in accordance with claim 3 wherein a portion of the R's are ozyhydrocarbon radicals in which the oxygen is part of an ester, ether or alcohol functionality.

5. A sustained release dispensing device in accordance with claim 1 , wherein the hydrophobic poly(carboxylic acid) comprises a polymer of maleic acid or the anhdride thereof acrlic acid or methacrlic acid.

6. A sustained release dispensing device in accordance with claim 1 wherein the hydrophobic poly(carboxyllc acid) is a terpolymer of at least one a, β-unsaturated aliphatic acid of 3 to 8 carbon atoms, and alkyl esters of such an a, β-unsaturated aliphatic acid in which said alkyl is of 2 to 8 carbon atoms.

7. A sustained release dispensing device in accordance with claim 1 wherein the hydrophobic poly(carboxylic acid) is a terpolymer comprising 60 to 75 mol# butyl aer late, 1 to 30 moljfa methacrylic acid and 5 to 15 olfo acrylic acid.

8. A sustained release dispensing device in accordance with claim 1 wherein the active agent is a drug and the essentially constant pH environment is located in a mammal.

9. A sustained release dispensing device in accordance with claim 1 wherein the active agent is a drug, the essentially constant pH environment is the ocular cavity of a mammal and the body is shaped for insertion in said ocular cavity.

10. A sustained, release dispensing device in accordance with claim 1 wherein ' the active agent is a drug, the essentially constant pH environment is the uterine cavity of a female mammal and the body is shaped for insertion in said uterine cavity..

11. A sustained release dispensing device in accordance with claim 1 wherein the device is .elongate and comprises two adjacent substantially parallel s.urfaces.

12. A sustained release dispensing device in accordance with claim 1 wherein the thickness of the device is less than 10^ of its other dimensions.

13. * A sustained release dispensing device in accordance with claim 1 wherein said body is in the form of layers of the same or different hydrophobic poly (carboxylic acid) said layers having the same or different active agent dispersed therethrough at the same or different concentrations. - - 43915/2

14. ·' A sustained release dispensing device in accordance with claim 6 wherein the essentially constant pH environment is the ocular cavity of a mammal, the body is shaped for insertion in said ocular cavity and the active agent is hydrocortisone, a pilocarpine salt or chloroamphenicol.

15. ; A sustained release dispensing device in accoccance with claim 10 wherein the active agent is progesterone or a prostaglandin*

16. A sustained release dispensing device as claimed in cihaim 1 and substantially as described in Figures 1 to 7 and 9 of the accompanying drawings.

17. A sustained release dispensing device as claimed in claim 1 and substantially as described in any of the specific Examples hereinbefore set forth.

18. A method for dispensing an active agent to an aqueous environment having an essentially constant pH in the range of 6 to 9 at a controlled rate over a prolonged period of time comprising introducing into said environment a body of a hydrophobic poly(carboxylic acid) having one ionizable carboxylic hydrogen atom for each 8 to 22 carbon atoms containing an active agent dispersed therethrough which body when in said environment erodes at a controlled rate over a prolonged period of time in response to the essentially constant pH environment by a process of carboxylic -hydrogen ionization, thereby dispensing the dispersed active agent to the environment.

19. A method for dispensing an active agent in accordance with claim 18 wherein the active agent is a drug and said environment is located in a mammal.

20. A method for dispensing an active agent in accordance with claim 18.': ' wherein the hydrophobic poly(carboxylic acid) is represented by the formula: wherein the R's represent, organic radicals independently selected to provide an average of from 8 to 22 carbon atoms for each carboxylic hydrogen atom "and n has a value providing an average molecular weight of from 15,000 to 500,000.

21. A method for dispensing an active agent in accordance with claim 18 wherein the hydrophobic poly(carboxylic acid) comprises a polymer of maleic acid or the anhydride thereof, acrylic acid or methacrylic acid.

22. A method for dispensing an active agent in accordance with claim 18 wherein the hydrophobic polymer is a terpolymer of at least one a, β-unsatu-rated aliphatic acid of 3 to 8 carbon atoms and alkyl esters of such α, β-unsaturated aliphatic add in which said alkyl is of 2 to 8 carbon atoms.

23. ' A method for dispensin an active agent in accordance with claim 18 wherein the hydrophobic polymer is a terpolymer comprising 60 to 75 mo¾¾ butyl aerylate, 1 to 30 moljo methacrylic acid and 5 to 15 mol$ acrylic acid.

24. A method for dispensing an active agent in accordance with claim 18 wherein the active agent is a drug, said environment is the ocular cavity of a mammal and the body is shaped for insertion in said. ocular cavity.

25. A method' for dispensing an active'agent in accordance with claim 18 vrherein the active agent is a drug, the environment is the uterine cavity of a female mammal and the body is shaped for insertion in said uterine cavity.

26. A method for dispensing an active agent in accordance with claim 18 wherein the hydrophobic poly(carboxylic acid) comprises a terpolymer of at least one a, β-unsaturated aliphatic acid of 3 to 8 carbon atoms and alkyl esters of such a, β-unsaturated aliphatic acids in which said alkyl is of 2 to 8 carbon atoms, the environment is the ocular cavity of a mammal, the body is shaped for insertion in said ocular cavity and the active agent is hydrocortisone, a pilocarpine salt or chloroamphenicol.

27. A method for dispensing an active agent in accordance with claim 18 wherein the environment is the uterine cavity of a female mammal, the body is shaped for insertion in said uterine cavity and the active agent is progesterone or a prostaglandin.

28. A method for dispensing an active agent as claimed in claim 18 and substantially as described in any of the specific examples hereinbefore set forth.